This proposal describes a 5-year training program for the development of an academic career as physician- scientist in cardiovascular medicine. The principal investigator has completed residency training in internal medicine, clinical cardiology fellowship training and two years of postdoctoral research under the mentorship of Ching-Pin Chang, MD, PhD. Dr. Chang is a recognized leader in the field of cardiac development, and runs an active laboratory with several postdoctoral scholars, all of whom he has assisted in obtaining independent research support. To complement Dr. Chang's background, co-mentorship will be provided by Dr. Michael Lpngaker, who has a long track record of successful mentoring. An advisory committee has been formed which includes Dr. Longaker, Dr. John Cooke, and Dr. Joseph Wu. My research proposal focuses on utilizing mouse genetics to dissect the role of VEGF signaling in vascular remodeling. We will build on preliminary data showing that adventitial VEGF signaling via the VEGF receptor VEGFR2 is critical for neointimal hyperplasia following vascular injury. The specific aims include: 1) defining the effect of VEGFRl signaling in neointimal hyperplasia, 2) examining the cellular responses of adventitial precursor cells to VEGFRl and VEGFR2 signaling, 3) examining the role of VEGFR2 signaling in a mouse model of atherosclerosis. These studies will be the first detailed analysis using genetic methods to inhibit VEGF signaling by specific VEGF receptors and in specific cell types. Stanford University offers an ideal environment to successfully train physician-scientists. Stanford offers deep scientific resources and a collaborative community. The department of cardiovascular medicine, in particular, has a strong commitment to nurturing young academic physician-scientists and offers the clinical flexibility to do so. RELEVANCE (See instructions): Coronary artery disease , the leading cause of death in the western world, is most often treated by percutaneous coronary intervention (PCI). The major clinical limitation to PCI is restenosis, and current anti- restenosis therapies have major drawbacks. By understanding the role of VEGF signaling in restenosis, we hope to design new, effective, and safer anti-restenosis therapies based on manipulation of VEGF activity. (End of Abstract)